Is WAS p.Ala124= (c.372G>A) pathogenic?

WAS p.Ala124= (c.372G>A) is classified Likely benign in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-17). Very rare (popmax 0.00245%, amr); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Ala124= (c.372G>A)?

WAS p.Ala124= (c.372G>A) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Ala124= (c.372G>A) in the general population?

WAS p.Ala124= (c.372G>A) is very rare (popmax 0.00245%, amr) (gnomAD).

WAS p.Ala124=

c.372G>A · rs1557006531 · VCV2924540

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00245%, amr)

Conditions

thrombocytopenia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP -3.1, phastCons 0.56
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00245% Admixed American · 1/40,772 alleles

Filtering AF 0.000107% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.2e-05%

Overall 0.000509% 6/1,179,084 alleles · very rare exomes 6/1,065,003 · genomes 0/114,081 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00245%	40,772
African / African-American	0.00176%	56,934
European (non-Finnish)	0.000455%	219,584

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: WAS
Protein: p.Ala124=
Coding: c.372G>A
MANE Select: NM_000377
dbSNP: rs1557006531
Type: single nucleotide variant
Location: chrX:48685745 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 124: the wh1 domain

Full WAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombocytopenia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked severe congenital neutropenia Wiskott-Aldrich syndrome

Similar variants

WAS p.Ala124Glu Uncertain significance ★ ⚠ same residue
WAS c.1339-2A>G Pathogenic/Likely pathogenic ★★ same condition
WAS c.1453+2T>C Pathogenic ★★ same condition
WAS c.273+1G>A Pathogenic ★★ same condition
WAS c.360+1G>A Pathogenic ★★ same condition
WAS c.559+5G>A Pathogenic ★★ same condition
WAS c.777+1G>A Pathogenic ★★ same condition
WAS c.778-6G>A Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/was-p-ala124 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown